A new mutation in mgrb mediating polymyxin resistance in Klebsiella variicola

Autor(es)

Lenzi, Michael H. ^[1] ; Martins, Willames M. B. S. ^{[1, 2]} ; Roch, Melanie ^{[3, 4]} ; Ramos, Patricia L. ^[5] ; Sands, Kirsty ^{[6, 2]} ; Cayo, Rodrigo ^[1] ; Walsh, Timothy R. ^[7] ; Andrey, Diego O. ^{[3, 4]} ; Gales, Ana C. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Internal Med, Div Infect Dis, Escola Paulista Med, UNIFESP, Sao Paulo, S - Brazil

^[2] Cardiff Univ, Dept Med Microbiol, Div Infect & Immun, Cardiff - Wales

^[3] Geneva Univ Hosp, Serv Infect Dis, Geneva - Switzerland

^[4] Fac Med, Geneva - Switzerland

^[5] Fundacao Parque Zool Sao Paulo FPZSP, Dept Pesquisas Aplicadas, Sao Paulo - Brazil

^[6] Univ Oxford, Dept Zool, Oxford - England

^[7] Univ Oxford, Ineos Oxford Inst Antimicrobial Res, Dept Zool, Oxford - England

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS; v. 58, n. 5 NOV 2021.
• Citações Web of Science: 0

Resumo

A B S T R A C T Polymyxin resistance is a public health concern - present in humans, animals and the environment - caused by chromosomal-encoding or plasmid-encoding mechanisms. Chromosomal alterations in MgrB are frequently detected in Klebsiella spp., but not yet reported and characterised in Klebsiella variicola ( K. variicola). This study performed microbiological and genomic characterisation of three polymyxinresistant K. variicola isolates (M14, M15 and M50) recovered from the microbiota of migratory birds in Brazil. The isolates were submitted to SpeI-PFGE, broth microdilution and whole genome sequencing using Illumina MiSeq for analysis of genetic relatedness, sequence typing and detection of antimicrobial resistance genes. K. variicola isolates belonged to two clones, and susceptibility tests showed resistance only for polymyxins. Sequences of chromosomal two-component systems (PmrAB, PhoPQ, RstAB, CrrAB) and MgrB were evaluated by blastN and blastP against a polymyxin-susceptible K. variicola (A58243), and mutations with biological effect were checked by the PROVEAN tool. K. variicola isolates belonged to two clones, and susceptibility tests showed resistance for polymyxins. In M14 and M15, phoQ deleterious mutations (D90N, I122S and G385S) were identified, while an mgrB variant containing a single deletion (C deletion on position 93) leading to the production of a non-functional protein was detected in M50. mgrB complementation studies showed restoration of polymyxin susceptibility (64 to <= 0.25 mg/L) as a wild-type mgrB was inserted into the mgrB-deficient M50. This study confirmed the role of a non-functional mgrB variant in conferring polymyxin resistance, stressing the role of this regulator in K. variicola and drawing attention to novel polymyxin resistance mechanisms emerging in wildlife. (c) 2021 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved. (AU)

• Processo FAPESP: 17/02258-6 - Avaliação do Papel da Ave Migratória Dendrocygna viduata na Disseminação de Bacilos Gram-negativos Resistentes a Antimicrobianos
• Beneficiário: Ana Cristina Gales
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/24431-4 - Investigação e caracterização de bacteriófagos com atividade lítica frente aos principais clones bacterianos epidêmicos em hospitais brasileiros
• Beneficiário: Willames Marcos Brasileiro da Silva Martins
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado